{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T02:13:01Z","timestamp":1792635181852,"version":"4.5.0"},"reference-count":26,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2018,2,20]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              We have recently found that 3 repeated doses (12\u00d710\n              <jats:sup>6<\/jats:sup>\n              each) of c\u2010kit\n              <jats:styled-content style=\"fixed-case\">\n                <jats:sup>POS<\/jats:sup>\n              <\/jats:styled-content>\n              cardiac progenitor cells (\n              <jats:styled-content style=\"fixed-case\">CPC<\/jats:styled-content>\n              s) were markedly more effective than a single dose of 12\u00d710\n              <jats:sup>6<\/jats:sup>\n              cells in alleviating postinfarction left ventricular dysfunction and remodeling. However, since the single\u2010dose group received only one third of the total number of\n              <jats:styled-content style=\"fixed-case\">CPC<\/jats:styled-content>\n              s given to the multiple\u2010dose group, it is unknown whether the superior therapeutic efficacy was caused by repeated treatments per se or by administration of a higher total number of\n              <jats:styled-content style=\"fixed-case\">CPC<\/jats:styled-content>\n              s. This issue has major clinical implications because multiple cell injections in patients pose significant challenges, which would be obviated by using 1 large injection. Accordingly, we determined whether the beneficial effects of 3 repeated\n              <jats:styled-content style=\"fixed-case\">CPC<\/jats:styled-content>\n              doses can be recapitulated by 1 large dose containing the same total number of cells.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Rats with a 30\u2010day\u2010old myocardial infarction received 3 echo\u2010guided intraventricular infusions, 35\u00a0days apart, of vehicle\u2010vehicle\u2010vehicle, 36\u00d710\n              <jats:sup>6<\/jats:sup>\n              <jats:styled-content style=\"fixed-case\">CPC<\/jats:styled-content>\n              s\u2010vehicle\u2010vehicle, or 3 equal doses of 12\u00d710\n              <jats:sup>6<\/jats:sup>\n              <jats:styled-content style=\"fixed-case\">CPC<\/jats:styled-content>\n              s. Infusion of a single, large dose of\n              <jats:styled-content style=\"fixed-case\">CPC<\/jats:styled-content>\n              s (36\u00d710\n              <jats:sup>6<\/jats:sup>\n              cells) produced an initial improvement in left ventricular function, but no further improvement was observed after the second and third infusions (both vehicle). In contrast, each of the 3 doses of\n              <jats:styled-content style=\"fixed-case\">CPC<\/jats:styled-content>\n              s (12\u00d710\n              <jats:sup>6<\/jats:sup>\n              ) caused a progressive improvement in left ventricular function, the cumulative magnitude of which was greater than with a single dose. Unlike the single dose, repeated doses reduced collagen content and immune cell infiltration.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Three repeated doses of\n              <jats:styled-content style=\"fixed-case\">CPC<\/jats:styled-content>\n              s are superior to 1 dose even though the total number of cells infused is the same, possibly because of greater antifibrotic and anti\u2010inflammatory actions.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.117.007400","type":"journal-article","created":{"date-parts":[[2018,2,14]],"date-time":"2018-02-14T01:10:55Z","timestamp":1518570655000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":59,"title":["Repeated Administrations of Cardiac Progenitor Cells Are Superior to a Single Administration of an Equivalent Cumulative Dose"],"prefix":"10.1161","volume":"7","author":[{"given":"Xian\u2010Liang","family":"Tang","sequence":"first","affiliation":[{"name":"Division of Cardiovascular Medicine and Institute of Molecular Cardiology, University of Louisville, KY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunichi","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine and Institute of Molecular Cardiology, University of Louisville, KY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianhong","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine and Institute of Molecular Cardiology, University of Louisville, KY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcin","family":"Wysoczynski","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine and Institute of Molecular Cardiology, University of Louisville, KY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna M.","family":"Gumpert","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine and Institute of Molecular Cardiology, University of Louisville, KY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen\u2010Jian","family":"Wu","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine and Institute of Molecular Cardiology, University of Louisville, KY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greg","family":"Hunt","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine and Institute of Molecular Cardiology, University of Louisville, KY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather","family":"Stowers","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine and Institute of Molecular Cardiology, University of Louisville, KY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinghui","family":"Ou","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine and Institute of Molecular Cardiology, University of Louisville, KY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Bolli","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine and Institute of Molecular Cardiology, University of Louisville, KY"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.117.310710"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2017.38"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.308937"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-017-0606-5"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0096725"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-013-0346-0"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.109.871905"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.115.307647"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.115.002210"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0405957102"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-011-0180-1"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2005.06.018"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00328-2"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI116608"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118093"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.101.25.2981"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.88.5.520"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.2000.279.4.H1679"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.561522"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.302317"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.113.301720"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.4137\/CMC.S33164"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvs018"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.trsl.2015.07.002"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.309001"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2017.01.048"}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.117.007400","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T11:10:29Z","timestamp":1715598629000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.117.007400"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,2,20]]},"references-count":26,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2018,2,20]]}},"alternative-id":["10.1161\/JAHA.117.007400"],"URL":"https:\/\/doi.org\/10.1161\/jaha.117.007400","relation":{},"ISSN":["2047-9980"],"issn-type":[{"value":"2047-9980","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,2,20]]},"assertion":[{"value":"2017-08-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-12-13","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-02-13","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e007400"}}